CA2848753C - Multimeric oligonucleotide compounds - Google Patents

Multimeric oligonucleotide compounds Download PDF

Info

Publication number
CA2848753C
CA2848753C CA2848753A CA2848753A CA2848753C CA 2848753 C CA2848753 C CA 2848753C CA 2848753 A CA2848753 A CA 2848753A CA 2848753 A CA2848753 A CA 2848753A CA 2848753 C CA2848753 C CA 2848753C
Authority
CA
Canada
Prior art keywords
compound
linker
oligonucleotide
nucleotides
target
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CA2848753A
Other languages
English (en)
French (fr)
Other versions
CA2848753A1 (en
Inventor
Eugen Uhlmann
Markus Weber
Romesh Subramanian
Thomas Dino Rockel
Arthur M. Krieg
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Translate Bio MA Inc
Original Assignee
Translate Bio MA Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Translate Bio MA Inc filed Critical Translate Bio MA Inc
Publication of CA2848753A1 publication Critical patent/CA2848753A1/en
Application granted granted Critical
Publication of CA2848753C publication Critical patent/CA2848753C/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C12N2310/113—Antisense targeting other non-coding nucleic acids, e.g. antagomirs
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/341—Gapmers, i.e. of the type ===---===
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/50—Physical structure
    • C12N2310/51—Physical structure in polymeric form, e.g. multimers, concatemers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/50—Physical structure
    • C12N2310/52—Physical structure branched

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Cardiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Diabetes (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Saccharide Compounds (AREA)
CA2848753A 2011-09-14 2012-09-14 Multimeric oligonucleotide compounds Active CA2848753C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161534561P 2011-09-14 2011-09-14
US61/534,561 2011-09-14
PCT/US2012/055535 WO2013040429A1 (en) 2011-09-14 2012-09-14 Multimeric oligonucleotide compounds

Publications (2)

Publication Number Publication Date
CA2848753A1 CA2848753A1 (en) 2013-03-21
CA2848753C true CA2848753C (en) 2022-07-26

Family

ID=47883790

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2848753A Active CA2848753C (en) 2011-09-14 2012-09-14 Multimeric oligonucleotide compounds

Country Status (9)

Country Link
US (5) US9580708B2 (enExample)
EP (2) EP3533873A1 (enExample)
JP (2) JP6129844B2 (enExample)
AU (2) AU2012308320C1 (enExample)
CA (1) CA2848753C (enExample)
DK (1) DK2756080T3 (enExample)
HK (1) HK1200484A1 (enExample)
IL (1) IL231535A0 (enExample)
WO (1) WO2013040429A1 (enExample)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12458604B2 (en) 2020-10-14 2025-11-04 The Trustees Of The University Of Pennsylvania Methods of lipid nanoparticle manufacture and compositions derived therefrom

Families Citing this family (73)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101141544B1 (ko) 2009-03-13 2012-05-03 한국과학기술원 에스아이알엔에이 다중 접합체 및 이의 제조방법
EP3260540A1 (en) 2010-11-12 2017-12-27 The General Hospital Corporation Polycomb-associated non-coding rnas
EP3533873A1 (en) 2011-09-14 2019-09-04 Translate Bio MA, Inc. Multimeric oligonucleotide compounds
JPWO2013089157A1 (ja) * 2011-12-12 2015-04-27 独立行政法人国立循環器病研究センター オリゴヌクレオチド、およびオリゴヌクレオチドを有効成分として含有する高脂血症治療剤
DK2850189T3 (en) 2012-05-16 2019-02-25 Translate Bio Ma Inc COMPOSITIONS AND PROCEDURES FOR MODULATING GENEPRESSION
DK2850186T3 (en) 2012-05-16 2019-04-08 Translate Bio Ma Inc COMPOSITIONS AND PROCEDURES FOR MODULATING SMN GENFAMILY EXPRESSION
EP2850182A4 (en) 2012-05-16 2016-01-20 Rana Therapeutics Inc COMPOSITIONS AND METHODS FOR MODULATING ATP2A2 GENE EXPRESSION
AU2013262709A1 (en) 2012-05-16 2015-01-22 Rana Therapeutics, Inc. Compositions and methods for modulating MECP2 expression
US10837014B2 (en) 2012-05-16 2020-11-17 Translate Bio Ma, Inc. Compositions and methods for modulating SMN gene family expression
CA2873769A1 (en) 2012-05-16 2013-11-21 Rana Therapeutics Inc. Compositions and methods for modulating hemoglobin gene family expression
KR20160074368A (ko) 2012-05-16 2016-06-28 라나 테라퓨틱스, 인크. Utrn 발현을 조절하기 위한 조성물 및 방법
WO2014043133A1 (en) * 2012-09-13 2014-03-20 Clontech Laboratories, Inc. Methods of depleting a target nucleic acid in a sample and kits for practicing the same
US20150247141A1 (en) 2012-09-14 2015-09-03 Rana Therapeutics, Inc. Multimeric oligonucleotide compounds
RU2015119411A (ru) * 2012-11-15 2017-01-10 Рош Инновейшен Сентер Копенгаген А/С Конъюгаты антисмысловых соединений, направленные на аполипопротеин в
CN104250298B (zh) * 2013-06-25 2018-02-06 浙江华谱新创科技有限公司 一种艾塞那肽高效分离纯化方法
CN105658797A (zh) * 2013-08-16 2016-06-08 Rana医疗有限公司 用于调节rna的组合物和方法
JP2016531570A (ja) 2013-08-16 2016-10-13 ラナ セラピューティクス インコーポレイテッド ユークロマチン領域を標的とするオリゴヌクレオチド
CA2921457A1 (en) * 2013-08-16 2015-02-19 Rana Therapeutics, Inc. Heterochromatin forming non-coding rnas
EP3060664B1 (en) * 2013-10-25 2021-07-07 Sanofi Microrna compounds and methods for modulating mir-21 activity
WO2015113922A1 (en) * 2014-01-30 2015-08-06 Roche Innovation Center Copenhagen A/S Poly oligomer compound with biocleavable conjugates
GB201408623D0 (en) * 2014-05-15 2014-07-02 Santaris Pharma As Oligomers and oligomer conjugates
CA2949104C (en) * 2014-05-23 2023-09-26 Genzyme Corporation Multiple oligonucleotide moieties on peptide carrier
US10434064B2 (en) 2014-06-04 2019-10-08 Exicure, Inc. Multivalent delivery of immune modulators by liposomal spherical nucleic acids for prophylactic or therapeutic applications
JP2017523790A (ja) 2014-08-07 2017-08-24 レグルス セラピューティクス インコーポレイテッド 代謝障害のためのマイクロｒｎａの標的化
CN106794256B (zh) 2014-08-19 2021-04-30 西北大学 蛋白质/寡核苷酸核-壳纳米颗粒治疗剂
EP3198012B1 (en) 2014-09-26 2019-09-04 University of Massachusetts Rna-modulating agents
EP3220895B1 (en) 2014-11-21 2022-08-31 Northwestern University The sequence-specific cellular uptake of spherical nucleic acid nanoparticle conjugates
GB201421379D0 (en) * 2014-12-02 2015-01-14 Isis Innovation Ltd And Medical Res Council Molecule
US10758558B2 (en) 2015-02-13 2020-09-01 Translate Bio Ma, Inc. Hybrid oligonucleotides and uses thereof
IL316159A (en) 2015-06-15 2024-12-01 Mpeg La Llc Defined Oligonucleotide Multimers and Methods for Manufacture Thereof
WO2017047741A1 (ja) * 2015-09-16 2017-03-23 日本新薬株式会社 筋萎縮症治療用アンチセンス核酸
JP2018528783A (ja) * 2015-09-25 2018-10-04 アイオーニス ファーマシューティカルズ， インコーポレーテッドＩｏｎｉｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． コンジュゲートアンチセンス化合物及びその使用
EP3985116A1 (en) 2015-10-15 2022-04-20 City of Hope Compounds and compositions including phosphorothioated oligodeoxynucleotide, and methods of use thereof
MX2018009090A (es) * 2016-01-26 2019-03-28 Nissan Chemical Corp Oligonucleótido de cadena simple.
KR102475301B1 (ko) 2016-04-08 2022-12-09 트랜슬레이트 바이오 인코포레이티드 다량체 코딩 핵산 및 그 용도
MA45602A (fr) * 2016-07-08 2019-05-15 Staten Biotechnology B V Anticorps anti-apoc3 et leurs méthodes d'utilisation
AU2017296195A1 (en) 2016-07-11 2019-01-24 Translate Bio Ma, Inc. Nucleic acid conjugates and uses thereof
US10465242B2 (en) * 2016-07-14 2019-11-05 University Of Utah Research Foundation Multi-sequence capture system
CN107630015B (zh) * 2016-07-19 2021-03-09 上海市东方医院 一种稳定的dna-rna双链结构
WO2018035380A1 (en) 2016-08-17 2018-02-22 Solstice Biologics, Ltd. Polynucleotide constructs
CN110177544A (zh) 2016-11-29 2019-08-27 普尔泰克健康有限公司 用于递送治疗剂的外泌体
CA3052038C (en) * 2017-01-31 2023-08-01 Curigin Co., Ltd. Nucleic acid simultaneously inhibiting expression of mtor gene and stat3 gene
CN110248665A (zh) 2017-02-06 2019-09-17 Mpeg La有限责任公司 具有降低的肾清除的多聚体寡核苷酸
EP3584319A4 (en) 2017-02-06 2021-04-14 Nissan Chemical Corporation SINGLE-STRAND OLIGONUCLEOTIDE
WO2018209270A1 (en) 2017-05-11 2018-11-15 Northwestern University Adoptive cell therapy using spherical nucleic acids (snas)
US11597744B2 (en) 2017-06-30 2023-03-07 Sirius Therapeutics, Inc. Chiral phosphoramidite auxiliaries and methods of their use
EP3447154A1 (en) * 2017-08-23 2019-02-27 Instytut Genetyki Sadowej Jolanta Powierska - Czarny Method for detection of mutations, polymorphisms and specific dna sequences on dna matrices with dna imaging techniques for the use in medical diagnostics and forensic genetics
JP6960641B2 (ja) * 2017-11-09 2021-11-05 国立大学法人 東京大学 ｍＲＮＡの安定化方法
EP3737424A4 (en) * 2018-01-10 2021-10-27 Translate Bio MA, Inc. COMPOSITIONS AND METHODS TO FACILITATE THE DELIVERY OF SYNTHETIC NUCLEIC ACIDS INTO CELLS
MX2020009765A (es) * 2018-03-20 2021-01-08 Tokyo Inst Tech Oligonucleotido antisentido reducido en toxicidad.
WO2019231299A1 (ko) * 2018-05-31 2019-12-05 고려대학교 산학협력단 마이크로rna를 억제하는 변형 핵산 및 이의 용도
WO2020018739A1 (en) 2018-07-18 2020-01-23 University Of Florida Research Foundation Rna silencing nanozymes
GB201812980D0 (en) 2018-08-09 2018-09-26 Univ Oxford Innovation Ltd Cell-penetrating peptides
GB201812972D0 (en) 2018-08-09 2018-09-26 Univ Oxford Innovation Ltd Cell-penetrating peptides
JP7661218B2 (ja) 2018-11-02 2025-04-14 バイオマリン テクノロジーズ ベー．フェー． ジストロフィンエクソンスキッピングのための二重特異性アンチセンスオリゴヌクレオチド
EP3890783A1 (en) 2018-12-07 2021-10-13 Oxford University Innovation Limited Linkers
US20220088202A1 (en) * 2019-01-23 2022-03-24 Shanghai Jiaotong University Nucleic Acid-Drug Conjugate, Drug Delivery System, Preparation Method Therefor and Use Thereof
CN113994004A (zh) * 2019-03-04 2022-01-28 Mpeg La有限责任公司 具有增强生物活性的多聚寡核苷酸
CN114072501A (zh) 2019-05-06 2022-02-18 马萨诸塞大学 抗c9orf72寡核苷酸及相关方法
WO2021026490A1 (en) * 2019-08-08 2021-02-11 Mpeg La, L.L.C. Cns targeting with multimeric oligonucleotides
CN115997019A (zh) * 2020-04-30 2023-04-21 Mpeg La有限责任公司 具有分链的多聚寡核苷酸
CA3178559A1 (en) * 2020-05-19 2021-11-25 Jonathan Miles Brown Orthogonally linked multimeric oligonucleotides
US20240318174A1 (en) * 2021-02-08 2024-09-26 Ractigen Therapeutics Multi-Valent Oligonucleotide Agent and Methods of Use Thereof
US20240327449A1 (en) * 2021-07-28 2024-10-03 The Regents Of The University Of California Structure-based design of antisense oligonucleotide drugs
US20230406888A1 (en) * 2022-04-27 2023-12-21 Sachi Bioworks Inc. Methods and systems for targeting autoimmune and inflammatory pathways using nanoligomers
WO2024026474A1 (en) 2022-07-29 2024-02-01 Regeneron Pharmaceuticals, Inc. Compositions and methods for transferrin receptor (tfr)-mediated delivery to the brain and muscle
EP4594520A2 (en) 2022-09-30 2025-08-06 Sixfold Bioscience Ltd. Compositions containing oligonucleotides with theranostic applications
WO2024086551A1 (en) * 2022-10-17 2024-04-25 University Of Massachusetts Conjugates of sirna and antisense oligonucleotides (sirnaso) and methods of use in gene silencing
US20240182561A1 (en) 2022-11-04 2024-06-06 Regeneron Pharmaceuticals, Inc. Calcium voltage-gated channel auxiliary subunit gamma 1 (cacng1) binding proteins and cacng1-mediated delivery to skeletal muscle
AU2023379457A1 (en) 2022-11-14 2025-05-15 Regeneron Pharmaceuticals, Inc. Compositions and methods for fibroblast growth factor receptor 3-mediated delivery to astrocytes
CN120936364A (zh) 2023-01-27 2025-11-11 瑞泽恩制药公司 修饰的弹状病毒糖蛋白及其用途
WO2024228030A2 (en) 2023-05-04 2024-11-07 Argonaute RNA Limited Dual silencing
WO2025111500A1 (en) * 2023-11-22 2025-05-30 Ionis Pharmaceuticals, Inc. Modulation of gene expression

Family Cites Families (253)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US4469863A (en) 1980-11-12 1984-09-04 Ts O Paul O P Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof
US5023243A (en) 1981-10-23 1991-06-11 Molecular Biosystems, Inc. Oligonucleotide therapeutic agent and method of making same
ATE75483T1 (de) 1981-10-23 1992-05-15 Molecular Biosystems Inc Oligonukleotides heilmittel und dessen herstellungsverfahren.
US4476301A (en) 1982-04-29 1984-10-09 Centre National De La Recherche Scientifique Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon
JPS5927900A (ja) 1982-08-09 1984-02-14 Wakunaga Seiyaku Kk 固定化オリゴヌクレオチド
FR2540122B1 (fr) 1983-01-27 1985-11-29 Centre Nat Rech Scient Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application
US4605735A (en) 1983-02-14 1986-08-12 Wakunaga Seiyaku Kabushiki Kaisha Oligonucleotide derivatives
US4948882A (en) 1983-02-22 1990-08-14 Syngene, Inc. Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis
US4824941A (en) 1983-03-10 1989-04-25 Julian Gordon Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems
DE3329892A1 (de) 1983-08-18 1985-03-07 Köster, Hubert, Prof. Dr., 2000 Hamburg Verfahren zur herstellung von oligonucleotiden
US4587044A (en) 1983-09-01 1986-05-06 The Johns Hopkins University Linkage of proteins to nucleic acids
US5118802A (en) 1983-12-20 1992-06-02 California Institute Of Technology DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside
US5550111A (en) 1984-07-11 1996-08-27 Temple University-Of The Commonwealth System Of Higher Education Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
US5430136A (en) 1984-10-16 1995-07-04 Chiron Corporation Oligonucleotides having selectably cleavable and/or abasic sites
US5258506A (en) 1984-10-16 1993-11-02 Chiron Corporation Photolabile reagents for incorporation into oligonucleotide chains
US4828979A (en) 1984-11-08 1989-05-09 Life Technologies, Inc. Nucleotide analogs for nucleic acid labeling and detection
FR2575751B1 (fr) 1985-01-08 1987-04-03 Pasteur Institut Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
US4762779A (en) 1985-06-13 1988-08-09 Amgen Inc. Compositions and methods for functionalizing nucleic acids
US5317098A (en) 1986-03-17 1994-05-31 Hiroaki Shizuya Non-radioisotope tagging of fragments
JPS638396A (ja) 1986-06-30 1988-01-14 Wakunaga Pharmaceut Co Ltd ポリ標識化オリゴヌクレオチド誘導体
EP0260032B1 (en) 1986-09-08 1994-01-26 Ajinomoto Co., Inc. Compounds for the cleavage at a specific position of RNA, oligomers employed for the formation of said compounds, and starting materials for the synthesis of said oligomers
US5276019A (en) 1987-03-25 1994-01-04 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US5264423A (en) 1987-03-25 1993-11-23 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
CA1340032C (en) 1987-06-24 1998-09-08 Jim Haralambidis Lucleoside derivatives
US5585481A (en) 1987-09-21 1996-12-17 Gen-Probe Incorporated Linking reagents for nucleotide probes
US4924624A (en) 1987-10-22 1990-05-15 Temple University-Of The Commonwealth System Of Higher Education 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
US5525465A (en) 1987-10-28 1996-06-11 Howard Florey Institute Of Experimental Physiology And Medicine Oligonucleotide-polyamide conjugates and methods of production and applications of the same
DE3738460A1 (de) 1987-11-12 1989-05-24 Max Planck Gesellschaft Modifizierte oligonukleotide
WO1989005358A1 (en) 1987-11-30 1989-06-15 University Of Iowa Research Foundation Dna and rna molecules stabilized by modifications of the 3'-terminal phosphodiester linkage and their use as nucleic acid probes and as therapeutic agents to block the expression of specifically targeted genes
US5403711A (en) 1987-11-30 1995-04-04 University Of Iowa Research Foundation Nucleic acid hybridization and amplification method for detection of specific sequences in which a complementary labeled nucleic acid probe is cleaved
US5082830A (en) 1988-02-26 1992-01-21 Enzo Biochem, Inc. End labeled nucleotide probe
WO1989009221A1 (en) 1988-03-25 1989-10-05 University Of Virginia Alumni Patents Foundation Oligonucleotide n-alkylphosphoramidates
US5278302A (en) 1988-05-26 1994-01-11 University Patents, Inc. Polynucleotide phosphorodithioates
US5109124A (en) 1988-06-01 1992-04-28 Biogen, Inc. Nucleic acid probe linked to a label having a terminal cysteine
US5216141A (en) 1988-06-06 1993-06-01 Benner Steven A Oligonucleotide analogs containing sulfur linkages
US5175273A (en) 1988-07-01 1992-12-29 Genentech, Inc. Nucleic acid intercalating agents
US5262536A (en) 1988-09-15 1993-11-16 E. I. Du Pont De Nemours And Company Reagents for the preparation of 5'-tagged oligonucleotides
US5512439A (en) 1988-11-21 1996-04-30 Dynal As Oligonucleotide-linked magnetic particles and uses thereof
US5599923A (en) 1989-03-06 1997-02-04 Board Of Regents, University Of Tx Texaphyrin metal complexes having improved functionalization
US5457183A (en) 1989-03-06 1995-10-10 Board Of Regents, The University Of Texas System Hydroxylated texaphyrins
US5391723A (en) 1989-05-31 1995-02-21 Neorx Corporation Oligonucleotide conjugates
US5256775A (en) 1989-06-05 1993-10-26 Gilead Sciences, Inc. Exonuclease-resistant oligonucleotides
US4958013A (en) 1989-06-06 1990-09-18 Northwestern University Cholesteryl modified oligonucleotides
US5451463A (en) 1989-08-28 1995-09-19 Clontech Laboratories, Inc. Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides
US5134066A (en) 1989-08-29 1992-07-28 Monsanto Company Improved probes using nucleosides containing 3-dezauracil analogs
US5254469A (en) 1989-09-12 1993-10-19 Eastman Kodak Company Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures
US5399676A (en) 1989-10-23 1995-03-21 Gilead Sciences Oligonucleotides with inverted polarity
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
US5292873A (en) 1989-11-29 1994-03-08 The Research Foundation Of State University Of New York Nucleic acids labeled with naphthoquinone probe
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5130302A (en) 1989-12-20 1992-07-14 Boron Bilogicals, Inc. Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
US6395492B1 (en) 1990-01-11 2002-05-28 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake and other properties
US6005087A (en) 1995-06-06 1999-12-21 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5623065A (en) 1990-08-13 1997-04-22 Isis Pharmaceuticals, Inc. Gapped 2' modified oligonucleotides
US6753423B1 (en) 1990-01-11 2004-06-22 Isis Pharmaceuticals, Inc. Compositions and methods for enhanced biostability and altered biodistribution of oligonucleotides in mammals
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
US5914396A (en) 1990-01-11 1999-06-22 Isis Pharmaceuticals, Inc. 2'-O-modified nucleosides and phosphoramidites
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5220007A (en) 1990-02-15 1993-06-15 The Worcester Foundation For Experimental Biology Method of site-specific alteration of RNA and production of encoded polypeptides
US5149797A (en) 1990-02-15 1992-09-22 The Worcester Foundation For Experimental Biology Method of site-specific alteration of rna and production of encoded polypeptides
US5214136A (en) 1990-02-20 1993-05-25 Gilead Sciences, Inc. Anthraquinone-derivatives oligonucleotides
AU7579991A (en) 1990-02-20 1991-09-18 Gilead Sciences, Inc. Pseudonucleosides and pseudonucleotides and their polymers
US5321131A (en) 1990-03-08 1994-06-14 Hybridon, Inc. Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling
US5470967A (en) 1990-04-10 1995-11-28 The Dupont Merck Pharmaceutical Company Oligonucleotide analogs with sulfamate linkages
DE69032425T2 (de) 1990-05-11 1998-11-26 Microprobe Corp., Bothell, Wash. Teststreifen zum Eintauchen für Nukleinsäure-Hybridisierungsassays und Verfahren zur kovalenten Immobilisierung von Oligonucleotiden
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5614617A (en) 1990-07-27 1997-03-25 Isis Pharmaceuticals, Inc. Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5688941A (en) 1990-07-27 1997-11-18 Isis Pharmaceuticals, Inc. Methods of making conjugated 4' desmethyl nucleoside analog compounds
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
PT98562B (pt) 1990-08-03 1999-01-29 Sanofi Sa Processo para a preparacao de composicoes que compreendem sequencias de nucleo-sidos com cerca de 6 a cerca de 200 bases resistentes a nucleases
US5245022A (en) 1990-08-03 1993-09-14 Sterling Drug, Inc. Exonuclease resistant terminally substituted oligonucleotides
US5177196A (en) 1990-08-16 1993-01-05 Microprobe Corporation Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof
US5512667A (en) 1990-08-28 1996-04-30 Reed; Michael W. Trifunctional intermediates for preparing 3'-tailed oligonucleotides
US5214134A (en) 1990-09-12 1993-05-25 Sterling Winthrop Inc. Process of linking nucleosides with a siloxane bridge
US5561225A (en) 1990-09-19 1996-10-01 Southern Research Institute Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages
AU662298B2 (en) 1990-09-20 1995-08-31 Gilead Sciences, Inc. Modified internucleoside linkages
US5432272A (en) 1990-10-09 1995-07-11 Benner; Steven A. Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases
EP0556301B1 (en) 1990-11-08 2001-01-10 Hybridon, Inc. Incorporation of multiple reporter groups on synthetic oligonucleotides
WO1994008003A1 (en) 1991-06-14 1994-04-14 Isis Pharmaceuticals, Inc. ANTISENSE OLIGONUCLEOTIDE INHIBITION OF THE ras GENE
US5965722A (en) 1991-05-21 1999-10-12 Isis Pharmaceuticals, Inc. Antisense inhibition of ras gene with chimeric and alternating oligonucleotides
US7015315B1 (en) 1991-12-24 2006-03-21 Isis Pharmaceuticals, Inc. Gapped oligonucleotides
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
US5719262A (en) 1993-11-22 1998-02-17 Buchardt, Deceased; Ole Peptide nucleic acids having amino acid side chains
US5714331A (en) 1991-05-24 1998-02-03 Buchardt, Deceased; Ole Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
US5371241A (en) 1991-07-19 1994-12-06 Pharmacia P-L Biochemicals Inc. Fluorescein labelled phosphoramidites
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
US5661134A (en) 1991-10-15 1997-08-26 Isis Pharmaceuticals, Inc. Oligonucleotides for modulating Ha-ras or Ki-ras having phosphorothioate linkages of high chiral purity
US6831166B2 (en) 1992-10-23 2004-12-14 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake and other properties
US8153602B1 (en) 1991-11-19 2012-04-10 Isis Pharmaceuticals, Inc. Composition and methods for the pulmonary delivery of nucleic acids
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
US5700922A (en) 1991-12-24 1997-12-23 Isis Pharmaceuticals, Inc. PNA-DNA-PNA chimeric macromolecules
DK0618925T4 (da) 1991-12-24 2012-07-09 Isis Pharmaceuticals Inc Antisense-oligonukleotider
US20060270624A1 (en) 1991-12-24 2006-11-30 Isis Pharmaceuticals, Inc. Gapped 2' modified oligonucleotides
US5565552A (en) 1992-01-21 1996-10-15 Pharmacyclics, Inc. Method of expanded porphyrin-oligonucleotide conjugate synthesis
US5595726A (en) 1992-01-21 1997-01-21 Pharmacyclics, Inc. Chromophore probe for detection of nucleic acid
US5633360A (en) 1992-04-14 1997-05-27 Gilead Sciences, Inc. Oligonucleotide analogs capable of passive cell membrane permeation
US5434257A (en) 1992-06-01 1995-07-18 Gilead Sciences, Inc. Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages
NL9300058A (nl) 1992-06-18 1994-01-17 Stichting Rega V Z W 1,5-anhydrohexitol nucleoside analoga en farmaceutisch gebruik daarvan.
US5272250A (en) 1992-07-10 1993-12-21 Spielvogel Bernard F Boronated phosphoramidate compounds
US5652355A (en) 1992-07-23 1997-07-29 Worcester Foundation For Experimental Biology Hybrid oligonucleotide phosphorothioates
TW244371B (enExample) 1992-07-23 1995-04-01 Tri Clover Inc
US6346614B1 (en) 1992-07-23 2002-02-12 Hybridon, Inc. Hybrid oligonucleotide phosphorothioates
EP0652890B1 (en) 1992-07-27 1998-01-14 HYBRIDON, Inc. Oligonucleotide alkylphosphonothioates
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
DE69400208T2 (de) 1993-01-25 1996-11-28 Hybridon Inc Olionukleotidalkylphosphonate und -phosphonothioate
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
ATE160572T1 (de) 1993-03-31 1997-12-15 Sanofi Sa Oligonucleotide mit amidverkettungen die phosphoesterverkettungen einsetzen
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
US5457187A (en) 1993-12-08 1995-10-10 Board Of Regents University Of Nebraska Oligonucleotides containing 5-fluorouracil
CA2178729A1 (en) 1993-12-09 1995-06-15 Eric B. Kmiec Compounds and methods for site-directed mutations in eukaryotic cells
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
US5625050A (en) 1994-03-31 1997-04-29 Amgen Inc. Modified oligonucleotides and intermediates useful in nucleic acid therapeutics
US5525711A (en) 1994-05-18 1996-06-11 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Pteridine nucleotide analogs as fluorescent DNA probes
US5597696A (en) 1994-07-18 1997-01-28 Becton Dickinson And Company Covalent cyanine dye oligonucleotide conjugates
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
US5734039A (en) 1994-09-15 1998-03-31 Thomas Jefferson University Antisense oligonucleotides targeting cooperating oncogenes
US6608035B1 (en) 1994-10-25 2003-08-19 Hybridon, Inc. Method of down-regulating gene expression
US5652356A (en) 1995-08-17 1997-07-29 Hybridon, Inc. Inverted chimeric and hybrid oligonucleotides
US8217015B2 (en) 2003-04-04 2012-07-10 Arrowhead Madison Inc. Endosomolytic polymers
CA2749312A1 (en) 1996-02-14 1997-08-21 Novartis Ag Sugar-modified gapped oligonucleotides
AU1874397A (en) 1996-02-16 1997-09-02 Stichting Rega Vzw Hexitol containing oligonucleotides and their use in antisense strategies
US6015710A (en) 1996-04-09 2000-01-18 The University Of Texas System Modulation of mammalian telomerase by peptide nucleic acids
US5898031A (en) 1996-06-06 1999-04-27 Isis Pharmaceuticals, Inc. Oligoribonucleotides for cleaving RNA
WO2005121370A2 (en) 2004-06-03 2005-12-22 Isis Pharmaceuticals, Inc. Oligomeric compounds that facilitate risc loading
US5912332A (en) 1996-07-26 1999-06-15 Hybridon, Inc. Affinity-based purification of oligonucleotides using soluble multimeric oligonucleotides
JP3756313B2 (ja) 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
US6383808B1 (en) 2000-09-11 2002-05-07 Isis Pharmaceuticals, Inc. Antisense inhibition of clusterin expression
EP1027364B1 (en) 1997-11-07 2004-12-08 Isis Pharmaceuticals, Inc. Pyrimidine derivatives for labeled binding partners
EP1071753A2 (en) 1998-04-20 2001-01-31 Ribozyme Pharmaceuticals, Inc. Nucleic acid molecules with novel chemical compositions capable of modulating gene expression
EP1088066B1 (en) 1998-06-19 2006-11-29 McGILL UNIVERSITY Antisense oligonucleotide constructs based on beta-arabinofuranose and its analogues
EP0979869A1 (en) * 1998-08-07 2000-02-16 Hoechst Marion Roussel Deutschland GmbH Short oligonucleotides for the inhibition of VEGF expression
US6228642B1 (en) 1998-10-05 2001-05-08 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of tumor necrosis factor-(α) (TNF-α) expression
US6210892B1 (en) 1998-10-07 2001-04-03 Isis Pharmaceuticals, Inc. Alteration of cellular behavior by antisense modulation of mRNA processing
US6465628B1 (en) 1999-02-04 2002-10-15 Isis Pharmaceuticals, Inc. Process for the synthesis of oligomeric compounds
ATE287897T2 (de) 1999-02-12 2005-02-15 Sankyo Co Analoga von nukleosiden und oligonukleotiden
KR20000065690A (ko) 1999-04-08 2000-11-15 박종구 반응 특이성 및 안정성을 개선시킨 안티센스 올리고 뉴클레오타이드, 안티센스 ｄｎａ 및 그 제조방법
US20080281041A1 (en) 1999-06-07 2008-11-13 Rozema David B Reversibly Masked Polymers
US6677445B1 (en) 1999-08-27 2004-01-13 Chiron Corporation Chimeric antisense oligonucleotides and cell transfecting formulations thereof
ATE269864T1 (de) 1999-09-10 2004-07-15 Stichting Rega V Z W Carbocyclische nukleoside und verfahren zu deren herstellung
WO2001025248A2 (en) 1999-10-04 2001-04-12 Exiqon A/S Design of high affinity rnase h recruiting oligonucleotide
US20020068709A1 (en) 1999-12-23 2002-06-06 Henrik Orum Therapeutic uses of LNA-modified oligonucleotides
EP1244667B1 (en) 1999-12-30 2006-04-05 K.U. Leuven Research & Development Cyclohexene nucleic acids
US6602857B1 (en) 2000-01-18 2003-08-05 Isis Pharmaceuticals, Inc. Antisense modulation of PTP1B expression
US6287860B1 (en) 2000-01-20 2001-09-11 Isis Pharmaceuticals, Inc. Antisense inhibition of MEKK2 expression
US6727355B2 (en) 2000-08-25 2004-04-27 Jcr Pharmaceuticals Co., Ltd. Pharmaceutical composition for treatment of Duchenne muscular dystrophy
ATE293688T1 (de) 2000-09-06 2005-05-15 Univ Mcgill Chimerische antisense-oligonukleotide aus arabinofuranose-analogen und deoxyribose- nukleotide
WO2002038738A2 (en) 2000-11-09 2002-05-16 Cold Spring Harbor Laboratory Chimeric molecules to modulate gene expression
ATE348104T1 (de) 2001-10-29 2007-01-15 Univ Mcgill Azyklische linker enthaltende oligonukleotide und deren verwendungen
US20030219402A1 (en) 2002-02-14 2003-11-27 Rutter William J. Chimeric molecules for cleavage in a treated host
US20080207542A1 (en) 2002-03-26 2008-08-28 Sirna Therapeutics, Inc. RNA inteference mediated inhibition of hepatitis C virus (HVC) gene expression using short interfering nucleic acid (siNA)
HUE037352T2 (hu) 2002-04-05 2018-08-28 Roche Innovation Ct Copenhagen As A HIF-1alfa expresszálódását módosító oligomer vegyületek
US20030228690A1 (en) 2002-06-10 2003-12-11 Isis Pharmaceuticals Inc. Antisense modulation of IL-1 receptor-associated kinase-1 expression
US7507808B2 (en) 2002-12-12 2009-03-24 Isis Pharmaceuticals, Inc. Modulation of endothelial lipase expression
US20050130924A1 (en) 2002-06-26 2005-06-16 Monia Brett P. Antisense inhibition via RNAse H-independent reduction in mRNA
WO2004044136A2 (en) 2002-11-05 2004-05-27 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2’-modified nucleosides for use in gene modulation
CA2506576C (en) 2002-11-18 2018-03-06 Santaris Pharma A/S Antisense gapmer oligonucleotides
CA2515644A1 (en) 2003-02-10 2004-08-19 Santaris Pharma A/S Oligomeric compounds for the modulation of ras expression
FR2853663B1 (fr) 2003-04-14 2007-08-31 Aventis Pharma Sa Procede d'obtention de lignees de mastocytes a partir de tissus de porcs et procede de production de molecules de type heparine
WO2004112565A2 (en) * 2003-06-25 2004-12-29 Quark Biotech, Inc. Diagnosis and treatment of liver, pulmonary and cardiac fibrosis
EP1648914A4 (en) 2003-07-31 2009-12-16 Regulus Therapeutics Inc OLIGOMERIC COMPOUNDS AND COMPOSITIONS USEFUL FOR MODULATING SMALL NON-CODING RNA
US20050053981A1 (en) 2003-09-09 2005-03-10 Swayze Eric E. Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini
GB0324854D0 (en) 2003-10-24 2003-11-26 Expresson Biosystems Ltd App/ena antisense
NZ546475A (en) 2003-10-30 2008-08-29 Coley Pharm Gmbh C-Class oligonucleotide analogs with enhanced immunostimulatory potency
US7431915B2 (en) 2003-10-31 2008-10-07 The Regents Of The University Of California Peptides whose uptake by cells is controllable
EP1706489B9 (en) 2003-12-23 2011-01-05 Santaris Pharma A/S Oligomeric compounds for the modulation of bcl-2
CA2553104A1 (en) 2004-01-23 2005-08-11 Avi Biopharma, Inc. Antisense oligomers and methods for inducing immune tolerance and immunosuppression
DE602005025347D1 (de) * 2004-01-30 2011-01-27 Quark Pharmaceuticals Inc Oligoribonukleotide und verfahren zu deren anwendung bei der behandlung von fibrotischen leiden und anderen krankheiten
US8314226B2 (en) 2004-03-29 2012-11-20 The General Hospital Corporation Oligonucleotide complex compositions and methods of use as gene alteration tools
AU2005248149A1 (en) 2004-05-26 2005-12-08 Rosetta Genomics Ltd. Viral and viral associated miRNAs and uses thereof
US7879992B2 (en) 2005-01-31 2011-02-01 Isis Pharmaceuticals, Inc. Modification of MyD88 splicing using modified oligonucleotides
CA2596506C (en) 2005-02-09 2021-04-06 Avi Biopharma, Inc. Antisense composition and method for treating muscle atrophy
DE102005036654A1 (de) 2005-08-04 2007-02-15 Bayer Materialscience Ag Selbstvernetzende PUR-Dispersionen mit Uretdionstruktur
WO2007056826A1 (en) 2005-11-21 2007-05-24 Johnson & Johnson Research Pty Limited Multitargeting interfering rnas and methods of their use and design
US20090011004A1 (en) 2005-12-30 2009-01-08 Philadelphia Health & Education Corp., D/B/A/ Drexel University Of College Of Medicine Improved carriers for delivery of nucleic acid agents to cells and tissues
AU2007211082B2 (en) 2006-01-27 2012-09-27 Isis Pharmaceuticals, Inc. Oligomeric compounds and compositions for the use in modulation of microRNAs
JP5342881B2 (ja) 2006-01-27 2013-11-13 アイシス ファーマシューティカルズ， インコーポレーテッド ６−修飾された二環式核酸類似体
US7569686B1 (en) 2006-01-27 2009-08-04 Isis Pharmaceuticals, Inc. Compounds and methods for synthesis of bicyclic nucleic acid analogs
US8362229B2 (en) * 2006-02-08 2013-01-29 Quark Pharmaceuticals, Inc. Tandem siRNAS
CA3024953A1 (en) 2006-04-03 2007-10-11 Roche Innovation Center Copenhagen A/S Pharmaceutical composition comprising anti-mirna antisense oligonucleotides
EP2505646A1 (en) 2006-05-05 2012-10-03 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of CRP
CN101500548A (zh) 2006-08-18 2009-08-05 弗·哈夫曼-拉罗切有限公司 用于体内递送多核苷酸的多缀合物
WO2008029619A1 (fr) 2006-09-07 2008-03-13 Daiichi Sankyo Company, Limited Oligonucléotide antisens ena ayant une action spécifique de la séquence
CA2666191C (en) 2006-10-09 2017-07-11 Santaris Pharma A/S Rna antagonist compounds for the modulation of pcsk9
JP5665317B2 (ja) 2006-10-18 2015-02-04 アイシス ファーマシューティカルズ， インコーポレーテッド アンチセンス化合物
US20080311040A1 (en) * 2007-03-06 2008-12-18 Flagship Ventures METHODS AND COMPOSITIONS FOR IMPROVED THERAPEUTIC EFFECTS WITH siRNA
DK2149605T3 (da) 2007-03-22 2013-09-30 Santaris Pharma As Korte RNA antagonist forbindelser til modulering af det ønskede mRNA
EP2179061B1 (en) 2007-08-15 2012-10-03 Idera Pharmaceuticals, Inc. Toll like receptor modulators
KR101889518B1 (ko) 2007-10-04 2018-08-17 로슈 이노베이션 센터 코펜하겐 에이/에스 마이크로ＭＩＲｓ
AU2008308499A1 (en) 2007-10-04 2009-04-09 Board Of Regents, The University Of Texas System Modulating gene expression with agRNA and gapmers targeting antisense transcripts
WO2009090182A1 (en) 2008-01-14 2009-07-23 Santaris Pharma A/S C4'-substituted - dna nucleotide gapmer oligonucleotides
WO2009109665A1 (en) 2008-03-07 2009-09-11 Santaris Pharma A/S Pharmaceutical compositions for treatment of microrna related diseases
US8846639B2 (en) 2008-04-04 2014-09-30 Isis Pharmaceutical, Inc. Oligomeric compounds comprising bicyclic nucleosides and having reduced toxicity
EP2268813A4 (en) 2008-04-07 2012-10-10 Univ Queensland RNA MOLECULES AND USES THEREOF
CA2635187A1 (en) 2008-06-05 2009-12-05 The Royal Institution For The Advancement Of Learning/Mcgill University Oligonucleotide duplexes and uses thereof
WO2010000665A1 (en) 2008-06-30 2010-01-07 Santaris Pharma A/S Antidote oligomers
EP2352830B1 (en) 2008-10-03 2019-01-16 CuRNA, Inc. Treatment of apolipoprotein-a1 related diseases by inhibition of natural antisense transcript to apolipoprotein-a1
CN104382853A (zh) * 2008-10-16 2015-03-04 玛瑞纳生物技术有限公司 基因沉默治疗剂的脂质体有效递送方法和组合物
CA2750561C (en) * 2009-01-26 2017-10-10 Protiva Biotherapeutics, Inc. Compositions and methods for silencing apolipoprotein c-iii expression
JP5529895B2 (ja) * 2009-02-04 2014-06-25 ソンギュングヮン ユニバーシティ ファウンデーション フォー コーポレート コラボレーション 細胞内の伝達能が増加した低分子干渉ｒｎａ複合体
WO2010093788A2 (en) * 2009-02-11 2010-08-19 Dicerna Pharmaceuticals, Inc. Multiplex dicer substrate rna interference molecules having joining sequences
WO2010120969A1 (en) 2009-04-15 2010-10-21 Board Of Regents, The University Of Texas System Targeting of the mir-30 family and let-7 family as a treatment for heart disease
EP2456470A1 (en) * 2009-07-22 2012-05-30 Cenix Bioscience GmbH Delivery system and conjugates for compound delivery via naturally occurring intracellular transport routes
PL2470656T3 (pl) * 2009-08-27 2015-08-31 Idera Pharmaceuticals Inc Kompozycja do hamowania ekspresji genów i jej zastosowanie
US9187746B2 (en) * 2009-09-22 2015-11-17 Alnylam Pharmaceuticals, Inc. Dual targeting siRNA agents
WO2011048125A1 (en) 2009-10-20 2011-04-28 Santaris Pharma A/S Oral delivery of therapeutically effective lna oligonucleotides
WO2011078672A1 (en) * 2009-12-24 2011-06-30 Prosensa Technologies B.V. Molecule for treating an inflammatory disorder
US20130079505A1 (en) 2010-03-24 2013-03-28 Mirrx Therapeutics A/S Bivalent antisense oligonucleotides
WO2011130371A1 (en) 2010-04-13 2011-10-20 Life Technologies Corporation Compositions and methods for inhibition of nucleic acids function
KR101860963B1 (ko) 2010-04-23 2018-05-24 제넨테크, 인크. 이종다량체 단백질의 생산
MX343559B (es) 2010-04-29 2016-11-10 Ionis Pharmaceuticals Inc Modulacion de la expresion de transtiretina.
EP2582397A4 (en) 2010-06-15 2014-10-29 Isis Pharmaceuticals Inc COMPOUNDS AND METHOD FOR MODULATING INTERACTION BETWEEN PROTEINS AND TARGET NUCLEIC ACIDS
GB201010557D0 (en) 2010-06-23 2010-08-11 Mina Therapeutics Ltd RNA molecules and uses thereof
AU2011282243B2 (en) 2010-07-19 2016-09-22 Ionis Pharmaceuticals, Inc. Modulation of nuclear-retained RNA
EP3260540A1 (en) 2010-11-12 2017-12-27 The General Hospital Corporation Polycomb-associated non-coding rnas
US10000752B2 (en) 2010-11-18 2018-06-19 Curna, Inc. Antagonat compositions and methods of use
EP2655621B1 (en) 2010-12-20 2018-05-23 The General Hospital Corporation Polycomb-associated non-coding rnas
US8557787B2 (en) * 2011-05-13 2013-10-15 The Board Of Trustees Of The Leland Stanford Junior University Diagnostic, prognostic and therapeutic uses of long non-coding RNAs for cancer and regenerative medicine
EP3533873A1 (en) 2011-09-14 2019-09-04 Translate Bio MA, Inc. Multimeric oligonucleotide compounds
US9209196B2 (en) 2011-11-30 2015-12-08 Sharp Kabushiki Kaisha Memory circuit, method of driving the same, nonvolatile storage device using the same, and liquid crystal display device
ES2765819T3 (es) 2012-03-04 2020-06-11 Bonac Corp Inhibidor de micro-ARN
BR112014028645A2 (pt) 2012-05-16 2017-06-27 Rana Therapeutics Inc composições e métodos para modulação da expressão de apoa1 e abca1.
DK2850189T3 (en) 2012-05-16 2019-02-25 Translate Bio Ma Inc COMPOSITIONS AND PROCEDURES FOR MODULATING GENEPRESSION
EP2850182A4 (en) 2012-05-16 2016-01-20 Rana Therapeutics Inc COMPOSITIONS AND METHODS FOR MODULATING ATP2A2 GENE EXPRESSION
WO2013173605A1 (en) 2012-05-16 2013-11-21 Rana Therapeutics, Inc. Compositions and methods for modulating pten expression
AU2013262709A1 (en) 2012-05-16 2015-01-22 Rana Therapeutics, Inc. Compositions and methods for modulating MECP2 expression
US9567581B2 (en) 2012-08-07 2017-02-14 The General Hospital Corporation Selective reactivation of genes on the inactive X chromosome
US20150247141A1 (en) 2012-09-14 2015-09-03 Rana Therapeutics, Inc. Multimeric oligonucleotide compounds
RU2015119411A (ru) 2012-11-15 2017-01-10 Рош Инновейшен Сентер Копенгаген А/С Конъюгаты антисмысловых соединений, направленные на аполипопротеин в
US9580078B2 (en) * 2014-09-25 2017-02-28 Toyota Motor Engineering & Manufacturing North America, Inc. Systems and methods for preheating hybrid vehicles
AU2015346042A1 (en) 2014-11-14 2017-04-27 Ionis Pharmaceuticals, Inc. Compounds and methods for the modulation of proteins

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12458604B2 (en) 2020-10-14 2025-11-04 The Trustees Of The University Of Pennsylvania Methods of lipid nanoparticle manufacture and compositions derived therefrom

Also Published As

Publication number Publication date
US20170211065A1 (en) 2017-07-27
US20150299695A1 (en) 2015-10-22
AU2018202634A1 (en) 2018-05-10
IL231535A0 (en) 2014-04-30
DK2756080T3 (da) 2019-05-20
AU2012308320B2 (en) 2018-02-15
CA2848753A1 (en) 2013-03-21
US10093924B2 (en) 2018-10-09
US20190062743A1 (en) 2019-02-28
US9732341B2 (en) 2017-08-15
JP2017127325A (ja) 2017-07-27
WO2013040429A1 (en) 2013-03-21
HK1200484A1 (zh) 2015-08-07
JP2014527819A (ja) 2014-10-23
US9732340B2 (en) 2017-08-15
US20150315587A1 (en) 2015-11-05
EP2756080B1 (en) 2019-02-20
US10704046B2 (en) 2020-07-07
EP2756080A1 (en) 2014-07-23
AU2018202634B2 (en) 2020-10-01
AU2012308320A1 (en) 2014-05-01
US9580708B2 (en) 2017-02-28
AU2012308320C1 (en) 2018-08-23
US20150315588A1 (en) 2015-11-05
EP2756080A4 (en) 2015-04-15
EP3533873A1 (en) 2019-09-04
JP6129844B2 (ja) 2017-05-17

Similar Documents

Publication Publication Date Title
AU2021203173B2 (en) Multimeric oligonucleotide compounds
AU2018202634B2 (en) Multimeric oligonucleotide compounds
EP2850186B1 (en) Compositions and methods for modulating smn gene family expression
JP2014527819A5 (enExample)
US20150225722A1 (en) Methods for selective targeting of heterochromatin forming non-coding rna
AU2014306416A9 (en) Compositions and methods for modulating RNA
JP2016531570A (ja) ユークロマチン領域を標的とするオリゴヌクレオチド
HK40013196A (en) Multimeric oligonucleotide compounds

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20170913

EEER Examination request

Effective date: 20170913